P1656: PROGRESSIVE WORSENING OF PROTHROMBOTIC PROFILE IN PATIENTS WITH AGGRESSIVE LYMPHOMA ON CHEMOTHERAPY
Authors: Francisco José López Jaime, Heidy Johana Campo Palacio, Kate Hurst, Manuel Espeso de Haro, Francisco Cabrera Ruiz, Alberto Doblas Márquez, Ihosvany Fernández Bello, Adrián Montaño
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Lymphoma patients have one of the highest incidences of thrombotic events among hematological malignancies. However, there are no well-defined protocols on the thromboprophylaxis strategies. Moreover, the thrombotic risk predictive models used in clinical routine, such as the one established by Khorana, have been shown not to be very specific for these patients. Recent studies have also reported that lymphoma patients present a state of hyperfibrinogemia that is associated with a worse prognosis. Nevertheless, the change of fibrinogen plasma levels and its effect on patients’ global hemostasis have not yet been addressed. Viscoelastic tests (VETs) have proven to be useful tools in the study of cancer associated hypercoagulability, including hematologic malignancies, but, as far as we know, there are no reported studies on the application of VETs in lymphoma patients. Aims: Analysis of the global hemostatic status of aggressive lymphoma patients at diagnosis and during the chemotherapy regimen using VETs. Methods: Samples from non-anticoagulated/antiaggregated aggressive lymphoma patients at diagnosis (T0), before the second (T1) and fifth (T2) cycle of chemotherapy were analyzed and compared with age-matched healthy controls. Thrombotic risk was evaluated according to the Khorana score. The global hemostatic analysis was evaluated by routine coagulation tests and VETs: thromboelastometry (ROTEM®) and Quantra®. Statistical analysis was performed using SPSS software. Results: Twenty aggressive lymphoma patients with a median age of 53 [minimum- maximum, 31-72] years were included. Seventy percent of patients (14/20) were women, with intermediate and high thrombotic risk in 90% (18/20) and 10% (2/20), respectively. At diagnosis, median fibrinogen levels were 357.8 [217-808] mg/dL compared to controls, 258 [211-294] mg/dL (P=0.036), highlighting that 40% (8/20) had levels above the normal range (>400 mg/dL). D-dimer levels were also significantly elevated compared to controls, 829.5 [347-3564] ng/mL vs. 280 ng/mL [155-530] (P=0.001). VET analysis revealed that lymphoma patients presented a hypercoagulable state at diagnosis characterized by increased clot stiffness (CS), mainly due to the contribution of fibrinogen (table 1). In fact, 60% of the patients (12/20) achieved ROTEM-fibTEM clotting amplitudes ≥ 20 mm compared with 0% in controls (P=0.007). Fibrinogen levels increased progressively during chemotherapy treatment reaching a median of 380.4 [293.6-506] mg/dL at T1 (vs. controls, P<0.001) and 418.8 [240.8-460.9] mg/dL at T2 (vs. controls, P<0.001). The same occurred with D-dimer, which remained elevated during treatment, reaching levels at T1 of 510 [210-1,170] ng/mL (vs. controls, P=0.012) and 830 [260-14,100] ng/mL at T2 (vs. controls, P=0.042). Consistent with this result, we observed a progressive increase in patients’ hypercoagulability during the treatment regimen (table 1). Fibrinogen levels were positively correlated with increased CS (r=0.818, P<0.001) by Quantra and the maximum clot firmness in FIBTEM (ROTEM) (r=0.747, P<0.001). No patient presented symptoms of thrombosis during the follow-up period of the study. Summary/Conclusion: A high percent of aggressive lymphoma patients presents a prothrombotic state at diagnosis that is aggravated during chemotherapy treatment. The identification of prognostic markers is necessary to help identify patients with a higher thrombotic risk and who could therefore be candidates for thromboprophylaxis. VETs prove to be powerful tools for determining and monitoring the global hemostatic status in lymphoma patients.Keywords: Lymphoma, Thromboembolism, Hemostasis, Thrombosis